This project studies the environmental and physiological regulation of the pineal gland. Major new discoveries within the last year were: (1) A reciprocal relationship exists between oxidation and N-acetylation products of serotonin in the pineal gland. At night the former are depressed and the latter are increased; the opposite is true during the day. Serotonin concentrations follow the pattern of oxidation products, and the major shifts appear to be regulated by serotonin N-acetyltransferase activity. This underlies the potential importance of N-acetylation of serotonin in regulating serotonin concentrations throughout the brain. (2) Melatonin production can be markedly increased by loading sheep with hydroxytryptophan. This observation raises the possibility that a pineal function test, based on the response of subjects to hydroxytryptophan, might be developed and used clinically. (3) A potent inhibitor of the nocturnal increase in melatonin was discovered: the alphal-adrenoceptor blocker prazosin. This points to the use of alpha adrenergic drugs to study melatonin production in humans, which has received little attention. (4) Pineal glands were successfully transplanted to the fourth ventricle. They continue to secrete melatonin, albeit at a reduced rate. Innervation takes place when superior cervical ganglia are cotransplanted; vascularization comes from surrounding brain. Using this approach it may be possible to learn how to construct an entire neural circuit, in this case the melatonin rhythm generating system. In addition, it should be possible to transplant genetically engineered pineal cells which produce novel compounds, including psychoactive chemicals, regulated by the adrenergic system which controls melatonin production.